Acute intake of ethanol has been shown to elicit a greater thermogenic response than the other energy -providing nutrients (carbohydrate and fat). The mechanisms behind this phenomenon remain incompletely understood. Several possibilities have been studied (MEOS metabolism, MEOS/ADH futile cycle, irreversible purine degradation); one possible contributor to the energetic inefficiency observed following acute ethanol consumption is ethanol stimulated biosynthesis, in particular lipogenesis, and substrate cycling. The hepatic lipogenic response to ethanol consumption has not been accurately measured to date. In this project, we propose to study the kinetic mechanisms underlying ethanol- induced changes in hepatic and whole-body lipid metabolism in humans by using recently developed stable isotope/mass spectrometric techniques. The specific questions to be addressed are: (l) What are the quantitative effects of ethanol ingestion on de novo hepatic lipogenesis (DNL), triglyceride production, fatty acid flux to the liver, and whole body fat oxidation? (2) What is the quantitative role of increased DNL in the thermogenic response to acute ethanol consumption? (3) What proportion of acetate derived from ethanol enters hepatic acetyl-CoA versus being exported into plasma as acetate, and does this correlate with lipogenesis or triglyceride synthesis? (4) What is the quantitative role of increased DNL in increased triglyceride production and decreased net fat oxidation? Non-alcoholic, regular, moderate consumers of ethanol will be studied (n=12). Subjects undergo three metabolic studies--two in the fasted state, one in the fed state. The two fasted state metabolic studies are one week apart to allow for isotopic washout. The first fasted metabolic study and the fed metabolic study will consist of an infusion of [1-13C]-acetate, [1,2,3,4 13C]-palmitate, and [2-13C]- glycerol. The second fasted state study will consist of an infusion of [1-13C]-ethanol; indirect calorimetry will be performed concurrently in all metabolic studies, By using these recently developed techniques, we hope to assess the role of ethanol stimulated lipogenesis in the thermogenic response to acute ethanol consumption as well as in whole body lipid metabolism and triglyceride secretion.